The Minichromosome maintenance family (MCM2-7) comprises a group of six structurally related proteins required to initiate DNA synthesis in eukaryotes (Kearsey et al., 1998). These proteins function in a complex very likely as a DNA helicase in promoting the opening of the DNA double helix at replication origins. ATP binding (Walker A) and hydrolysis (Walker B) motifs are present in all MCM2-7 members, embedded in a region which is highly conserved in this protein family, also known as the MCM2-7 signature domain (Koonin, 1993). Recently, this protein family has expanded by the identification of a novel member, the MCM8 protein (Gozuacik et al., 2003, Johnson et al., 2003, Maiorano et al., 2005). Unlike MCM2-7, which are widely conserved in eukaryotes, MCM8 is present only in higher multicellular organisms, being absent in worms and yeast.
Very recently, another new member of the MCM protein family, the MCM9 protein, has been identified in humans (Yoshida, 2005). Intriguingly, the predicted human protein (HsMCM9) has been reported to be a rather short homolog of MCM proteins (391 aa against an average of 800 aa in MCM2-7 and MCM8 proteins) and the function of this protein is not known.
Anomalies during DNA replication process are involved in different pathologies such as brains diseases, haematological disorders and cancers. Thus, means to control cellular division would be useful tools for the treatment of pathologies linked to a dysfunction of DNA replication or for pathologies linked to an excessive cellular proliferation.
One of the aims of the invention is to provide a pharmaceutical composition for treating pathologies linked to a dysfunction of DNA replication or to an excessive cell proliferation.
One of the aims of the invention is to provide a method for inhibiting cell proliferation or enhancing DNA replication.
One of the aims of the invention is to provide a method for screening drugs useful in the treatment of pathologies linked to a dysfunction of the replication or to an excessive cell proliferation.
Another aspect of the invention relates to the identification of a MCM2-8 family protein, for which only a truncated form was known, and its specific function.
All these aspects have been obtained by the identification of the full-length MCM9 gene and MCM9 protein.